Surface modification of contact lenses

ABSTRACT

Provided are surface modified contact lenses formed from one or more fumaric- or itaconic-containing prepolymers having reactive functionality that is complimentary to reactive hydrophilic polymers.

FIELD OF THE INVENTION

The present invention relates generally to reactive fumaric- anditaconic-containing prepolymers and compositions comprising theprepolymers used in the manufacture of medical devices. Morespecifically, the present invention relates to surface modified contactlenses formed from one or more functionalized fumaric- oritaconic-containing prepolymers having reactive functionality that iscomplimentary to reactive, hydrophilic polymers.

BACKGROUND OF THE INVENTION

Medical devices such as ophthalmic lenses made from silicone-containingmaterials have been investigated for a number of years. Such materialscan generally be sub-divided into two major classes, namely hydrogelsand non-hydrogels. Non-hydrogels do not absorb appreciable amounts ofwater, whereas hydrogels can absorb and retain water in an equilibriumstate. Hydrogels generally have water content between about 15 to about80 weight percent. Regardless of their water content, both non-hydrogeland hydrogel silicone medical devices tend to have relativelyhydrophobic, non-wettable surfaces that have a high affinity for lipids.This problem is of particular concern with contact lenses.

Fumarate- and fumaramide-containing monomers and compositions comprisingthe monomers have been developed to make highly oxygen permeablehydrogels which may be used to make biomedical devices including contactlenses. Examples of these fumarate- and fumaramide-containing monomersand compositions can be found in U.S. Pat. Nos. 5,374,662, 5,420,324,and 5,496,871, the contents of each being incorporated by referenceherein. Because of the polar character of amide functionality, thisclass of monomer shows good compatibility with both hydrophobic monomerssuch as tris(trimethylsiloxy)silane (TRIS) and hydrophilic monomers suchas N,N-dimethylacrylamide (DMA). These prior art prepolymers givesilicone hydrogels with excellent oxygen permeability and mechanicalproperties. However, like other silicone hydrogels, they are notwettable enough to be useful as continuous wear lenses unless thesurface is treated.

Surface structure and composition determine many of the physicalproperties and ultimate uses of solid materials. Characteristics such aswetting, friction, and adhesion or lubricity are largely influenced bysurface characteristics. The alteration of surface characteristics is ofspecial significance in biotechnical applications where biocompatibilityis of particular concern. Therefore, those skilled in the art have longrecognized the need for rendering the surface of contact lenses andother medical devices hydrophilic or more hydrophilic. Increasing thehydrophilicity of the contact-lens surface improves the wettability ofthe contact lenses with tear fluid in the eye. This in turn improves thewear comfort of the contact lenses. In the case of continuous-wearlenses, the surface is especially important. The surface of acontinuous-wear lens must be designed not only for comfort, but to avoidadverse reactions such as corneal edema, inflammation, or lymphocyteinfiltration. Improved methods have accordingly been sought formodifying the surfaces of contact lenses, particularly high-Dk (highlyoxygen permeable) lenses designed for continuous (overnight) wear.

Various patents disclose the attachment of hydrophilic or otherwisebiocompatible polymeric chains to the surface of a contact lens in orderto render the lens more biocompatible. For example, U.S. Pat. Pub. No.U.S. 2002/0102415 A1 teaches plasma treatment of a fumarate- orfumaramide-containing substrate followed by reaction with otherpolymers, such as DMA/VDMO copolymer.

Although manufacturing steps such as plasma treatment provide lenseshaving suitable coatings, it would be desirable to produce a surfacetreated lens without the need for plasma treatment or corona dischargetreatment.

It would be further desirable to provide an improved silicone hydrogelcontact lens with an optically clear, hydrophilic surface film that willnot only exhibit improved wettability, but which will generally allowthe use of a silicone hydrogel contact lens in the human eye for anextended period of time. In the case of a silicone hydrogel lens forextended wear, it would be desirable to provide a contact lens with asurface that is also highly permeable to oxygen and water. Such asurface treated lens would be comfortable to wear in actual use andwould allow for the extended wear of the lens without irritation orother adverse effects to the cornea.

SUMMARY OF THE INVENTION

In accordance with the present invention, reactive functionalizedfumaric- and itaconic-containing prepolymers are disclosed for use withboth silicone and non-silicone containing polymeric systems used forbiomedical devices, especially contact lenses. The prepolymers have thefollowing schematic representations:YCO—CH═CHCOW(R₁)_(n)(SiR₂R₃O)_(m)(SiR₂R₃)(R₁)_(n)WOCCH═CH—COYandCH₂═C(CH₂COY)COW(R₁)_(n)(SiR₂R₃O)_(m)(SiR₂R₃)(R₁)_(n)WOC(CH₂COY)C═CH₂wherein R₁ is an alkylene that may have ether linkages, R₂ and R₃ areindependently alkyl or phenyl groups, unsubstituted or substituted withhalogen and ether linkages, W is O or NH, n is an integer between 1 and10, m is an integer between 2 and 200, and Y is a residue having areactive functional group selected from the group consisting ofhydroxyl, carboxyl, oxazolone, epoxy and anhydride functional groups.The reactive functional group has complementary reactivity to reactivehydrophilic coating polymers.

The invention is further directed toward medical devices formed of apolymerizable mix comprising the reactive functionalized fumaric- anditaconic-containing prepolymers. Such devices are useful in formingsurface modified medical devices without use of treatments such asplasma treatment or corona discharge treatment.

This invention is further directed toward surface treatment of a devicecontaining the prepolymers disclosed herein, for example, siliconecontact lenses and other silicone medical devices, including a method ofmodifying the surface of a contact lens to increase its hydrophilicityor wettability. The surface treatment comprises the attachment ofhydrophilic reactive polymer chains to the surface of the contact lenssubstrate by means of reactive functionalities of the reactivefunctionalized fumaric- or itaconic-containing prepolymer component inthe lens substrate material reacting with complementary reactivefunctionalities in monomeric units along a hydrophilic reactive polymer.Such surface modification of a contact lens provides a lens havingimproved compatibility with the eye.

The present invention is also directed to a surface modified medicaldevice, examples of which include contact lenses, intraocular lenses,catheters, implants, and the like, comprising a surface made by such amethod.

DETAILED DESCRIPTION OF THE INVENTION

As stated above, the present invention is directed toward reactivefumaric- and itaconic-containing prepolymers for use withcopolymerizable polymeric systems used for biomedical devices,especially contact lenses. As used herein, fumaric refers to aderivative of fumaric acid and can be a fumarate (an ester), afumaramide (an amide) or a residue having both ester and amidefunctionalities. The fumaric group is a residue oftrans-1,2-ethylenedicarboxylate. Therefore, it will be understood thatthe diastereoisomer of fumarate, maleate, is also intended to beincluded in the fumaric-containing prepolymers of the present invention.Itaconic refers to derivatives of itaconic acid and has a similarmeaning as that of fumaric. In further embodiments of the presentinvention, the prepolymers are used to make biomedical devices and areuseful in contact lens formulations which may be either “soft” or “hard”and which may preferably be hydrogels.

In further embodiments of the present invention, medical devices madewith the prepolymers are coated with hydrophilic reactive polymer withcomplimentary reactive functionalities to the reactive functionalizedfumaric- and itaconic-containing medical devices.

The reactive functionalized fumaric- and itaconic-containing prepolymersof the present invention have at least one fumaric or itaconic group.Monomer mixes comprising the prepolymers of the present invention maycomprise both thermal- and photoinitiators for curing purposes. Themonomer mixes may further comprise at least one additional hydrophilicmonomer. Further, the monomer mix may additionally comprise at least onesilicone-containing monomer.

As is known in the field, certain crosslinked polymeric materials may bepolymerized to form a hard, water-free, xerogel. Xerogels are understoodto be unhydrated hydrogel formulations. It was found that such xerogelscould be physically altered to, for example, impart optical propertiesthrough machining, and then be hydrated and retain their water content.

When the term “polymerization” is used herein we refer to thepolymerization of the double bonds of the monomers and prepolymersendcapped with polymerizable unsaturated groups which results in acrosslinked three-dimensional network.

Further, notations such as “(meth)acrylate” or “(meth)acrylamide” areused herein to denote optional methyl substitution. Thus, for example,(meth)acrylate includes both acrylate and methacrylate andN-alkyl-(meth)acrylamide includes both N-alkyl acrylamide and N-alkylmethacrylamide.

The term “prepolymer” denotes a high molecular weight monomer containingpolymerizable groups. The monomers added to the monomeric mixture of thepresent invention may therefore be low molecular weight monomers orprepolymers. Thus, it is understood that a term such as“silicone-containing monomers” includes “silicone-containingprepolymers”.

The terms “shaped articles for use in biomedical applications” or“biomedical devices or materials” or “biocompatible materials” mean thehydrogel materials disclosed herein have physicochemical propertiesrendering them suitable for prolonged contact with living tissue, bloodand the mucous membranes.

While the present invention contemplates the use of reactivefunctionalized fumaric- and itaconic-containing prepolymers for medicaldevices including both “hard” and “soft” contact lenses, theformulations containing the reactive functionalized fumaric- anditaconic-containing prepolymers of the present invention are thought tobe especially useful as soft hydrogel contact lenses. As is understoodin the field, a lens is considered to be “soft” if it can be folded backupon itself without breaking.

A hydrogel is a hydrated cross-linked polymeric system that containswater in an equilibrium state. Silicone hydrogels (i.e., hydrogelscontaining silicone) are usually prepared by polymerizing a mixturecontaining at least one silicone-containing monomer and at least onehydrophilic monomer. By the term silicone, it is meant that the materialis an organic polymer comprising at least five percent by weightsilicone (—OSi— linkages), preferably 10 to 100 percent by weightsilicone, more preferably 30 to 90 percent by weight silicone.Applicable silicone-containing monomeric units for use in the formationof silicone hydrogels are well known in the art and numerous examplesare provided in U.S. Pat. Nos. 4,136,250; 4,153,641; 4,740,533;5,034,461; 5,070,215; 5,260,000; 5,310,779; and 5,358,995.

The reactive functionalized fumaric- and itaconic-containing prepolymersof the present invention have at least one fumaric or itaconic group.Monomer mixes comprising the prepolymers of the present invention maycomprise both thermal- and photoinitiators for curing purposes. Themonomer mixes may further comprise at least one additional hydrophilicmonomer. Further, the monomer mix may additionally comprise at least onesilicone-containing monomer.

The fumaric- and itaconic-containing prepolymers of the presentinvention are prepared according to syntheses well known in the art andaccording to the examples disclosed herein. The functionalized fumaric-and itaconic-containing prepolymers of the present invention areincorporated into the monomer mix. The relative weight % of thefunctionalized fumaric- and itaconic-containing prepolymers as comparedto the total monomer mix weight % is from about 10% to 80%, morepreferably from about 10% to 50%, and most preferably 15% to 40%.

Examples of hydrophilic monomers include, but are not limited to,ethylenically unsaturated lactam-containing monomers such as N-vinylpyrrolidinone; methacrylic and acrylic acids; (meth)acrylic substitutedalcohols, such as 2-hydroxyethylmethacrylate (HEMA) and2-hydroxyethylacrylate; and (meth)acrylamides, such as methacrylamideand N,N-dimethylacrylamide (DMA); vinyl carbonate or vinyl carbamatemonomers such as disclosed in U.S. Pat. No. 5,070,215; and oxazolinonemonomers such as disclosed in U.S. Pat. No. 4,910,277. Other hydrophilicmonomers such as glycerol methacrylate and polyethyleneglycolmonomethacrylate are also useful in the present invention.

Preferred hydrophilic vinyl-containing monomers that may be incorporatedinto the hydrogels of the present invention include monomers such asN-vinyl lactams such as N-vinyl pyrrolidinone (NVP), N-vinyl-N-methylacetamide, N-vinyl-N-ethyl acetamide, N-vinyl-N-ethyl formamide, N-vinylformamide, with NVP being the most preferred.

Preferred hydrophilic acrylic-containing monomers which may beincorporated into the hydrogel of the present invention includehydrophilic monomers such as N,N-dimethyl acrylamide (DMA),2-hydroxyethyl methacrylate, glycerol methacrylate, 2-hydroxyethylmethacrylamide, methacrylic acid and acrylic acid, with DMA being themost preferred. Other suitable hydrophilic monomers will be apparent toone skilled in the art. The relative weight % of hydrophilic monomer(s)to total weight % of the comonomer mix is preferably from about 5% to80%, more preferably from about 20% to 70%, and most preferably 20% to40%.

As mentioned previously, additional silicone-containing monomers may bepresent in the monomer mixes with the reactive functionalized fumaric-or itaconic-containing monomers. One preferred class of suitablesilicone-containing monomers which may be incorporated into a monomermix with the reactive functionalized fumaric- or itaconic-containingprepolymers of the present invention are the bulky polysiloxanylalkyl(meth)acrylic monomers represented by the following Formula (I):

wherein: X is O or NR; each R₁₅ is independently hydrogen or an alkylgroup having 1 to 10 carbon atoms; and each R₁₆ is independently a loweralkyl or phenyl group; and f is 1 or 3 to 10.

Such bulky monomers include methacryloxypropyltris(trimethylsiloxy)silane (TRIS),pentamethyldisiloxanylmethylmethacrylate,tris(trimethylsiloxy)methacryloxy propylsilane,phenyltetramethyldisiloxanylethyl acrylate, andmethyldi(trimethylsiloxy)methacryloxymethyl silane. Further preferredclasses of silicone-containing monomers which may be incorporated into amonomer mix with the reactive functionalized fumaric- oritaconic-containing monomers of the present invention are thepoly(organosiloxane) monomers represented by the following formula (II):

wherein: A is an activated unsaturated group, such as an ester or amideof an acrylic or a methacrylic acid; each R₂₃–R₂₆ is independentlyselected from the group consisting of a monovalent hydrocarbon radicalor a halogen substituted monovalent hydrocarbon radical having 1 to 18carbon atoms which may have ether linkages between carbon atoms; R₂₇ isa divalent hydrocarbon radical having from 1 to 22 carbon atoms; and nis 0 or an integer greater than or equal to 1. When siloxane-containingmonomers other than the functionalized silicone containing prepolymersare incorporated into the monomer mix, the weight % of the othersiloxane-containing monomers as compared to the total monomer mix weight% is from about 5% to 60%, more preferably from about 10% to 50%, andmost preferably 10% to 40%.

Either the silicone-containing monomer, the functionalized fumaric- oritaconic-containing prepolymer, or the hydrophilic monomer may functionas a crosslinking agent (a crosslinker), being defined as a monomerhaving multiple polymerizable functionalities. Additional crosslinkersalso may be present in the monomer mix which polymerizes to form thehydrogel.

Most “known” crosslinking agents are hydrophobic. When it is desirablefor both an acrylic-containing monomer and a vinyl-containing monomer tobe incorporated into the silicone-containing polymer of the presentinvention, a further crosslinking agent having both a vinyl and anacrylic polymerizable group may be used, since these vinyl and acrylicmonomers have differing reactivity ratios and may not copolymerizeefficiently. Such crosslinkers which facilitate the copolymerization ofthese monomers are the subject of U.S. Pat. No. 5,310,779, the contentsof which is incorporated herein by reference. Such crosslinkers arerepresented by the following schematic representation:

wherein V denotes a vinyl-containing group having the formula:

A denotes an acrylic-containing group having the formula:

S denotes a styrene-containing group having the formula:

wherein R₃₁ is an alkyl radical derived from substituted andunsubstituted hydrocarbons, polyalkylene oxide, poly(perfluoro) alkyleneoxide, dialkyl-capped polydimethylsiloxane, dialkyl-cappedpolydimethylsiloxane modified with fluoroalkyl or fluoroether groups;R₃₂–R₄₀ are independently H, or alkyl of 1 to 5 carbon atoms; Q is anorganic group containing aromatic moieties having 6–30 carbon atoms; X,Y, and Z are independently O, NH or S; v is 1, or higher; and a, s areindependently greater than or equal to 0; and a+s is greater than orequal to 1. An example is 2-hydroxyethylmethacrylate vinyl carbonate orcarbamate.

Other crosslinking agents which may be incorporated into thesilicone-containing hydrogel of the present invention include polyvinyl,typically di- or tri-vinyl monomers, most commonly the di- ortri(meth)acrylates of dihydric ethylene glycol, triethylene glycol,butylene glycol, hexane-1,6-diol, thio-diethylene glycol-diacrylate andmethacrylate; neopentyl glycol diacrylate; trimethylolpropanetriacrylate and the like; N,N′-dihydroxyethylene-bisacrylamide and-bismethacrylamides; also diallyl compounds like diallyl phthalate andtriallyl cyanurate; divinylbenzene; ethylene glycol divinyl ether; andthe (meth)acrylate esters of polyols such as triethanolamine, glycerol,pentaerythritol, butylene glycol, mannitol, and sorbitol. Furtherexamples include N,N-methylene-bis-(meth)acrylamide, sulfonateddivinylbenzene, and divinylsulfone. Also useful are the reactionproducts of hydroxyalkyl (meth)acrylates with unsaturated isocyanates,for example the reaction product of 2-hydroxyethyl methacrylate with2-isocyanatoethyl methacrylate (IEM). See U.S. Pat. No. 4,954,587.

Other known crosslinking agents arepolyether-bisurethane-dimethacrylates (see U.S. Pat. No. 4,192,827), andthose crosslinkers obtained by reaction of polyethylene glycol,polypropylene glycol and polytetramethylene glycol with2-isocyanatoethyl methacrylate (IEM) or m-isopropenyl-γ,γ-dimethylbenzylisocyanates (m-TMI), and polysiloxane-bisurethane-dimethacrylates. SeeU.S. Pat. Nos. 4,486,577 and 4,605,712. Still other known crosslinkingagents are the reaction products of polyvinyl alcohol, ethoxylatedpolyvinyl alcohol or of polyvinyl alcohol-co-ethylene with 0.1 to 10 mol% vinyl isocyanates like IEM or m-TMI.

The prepolymers of the present invention, when copolymerized, arereadily cured to cast shapes by methods such as UV polymerization, useof free radical thermal initiators and heat, or combinations thereof.Representative free radical thermal polymerization initiators areorganic peroxides, such as for example acetyl peroxide, lauroylperoxide, decanoyl peroxide, stearoyl peroxide, benzoyl peroxide,tertiary butyl peroxypivalate, peroxydicarbonate, and the commerciallyavailable thermal initiators such as LUPERSOL® 256, 225 (AtofinaChemical, Philadelphia, Pa.) and the like, employed in a concentrationof about 0.01 to 2 percent by weight of the total monomer mixture.Representative UV initiators are those known in the field such as,benzoin methyl ether, benzoin ethyl ether, DAROCUR®-1173, 1164, 2273,1116, 2959, 3331, IGRACURE® 651 and 184 (Ciba Specialty Chemicals,Ardsley, N.Y.).

In addition to the above-mentioned polymerization initiators, thecopolymer of the present invention may also include other components aswill be apparent to one skilled in the art. For example, the monomer mixmay include additional colorants, or UV-absorbing agents and tougheningagents such as those known in the contact lens art.

The resulting copolymers of this invention can be formed into contactlenses by the spincasting processes such as those disclosed in U.S. Pat.Nos. 3,408,429 and 3,496,254, static casting processes such as in U.S.Pat. No. 5,271,875 and other conventional methods, such as compressionmolding as disclosed in U.S. Pat. Nos. 4,084,459 and 4,197,266.

Polymerization of the monomer mix may be conducted either in a spinningmold, or a stationary mold corresponding to a desired contact lensshape. The thus-obtained contact lens may be further subjected to amechanical finishing, as occasion demands. Also, the polymerization maybe conducted in an appropriate mold or vessel to give a lens material inthe form of button, plate or rod, which may then be processed (e.g., cutor polished via lathe or laser) to give a contact lens having a desiredshape.

The hydrogels produced by the present invention are oxygen transporting,hydrolytically stable, biologically inert, and transparent. The monomersand prepolymers employed in accordance with this invention are readilypolymerized to form three-dimensional networks which permit thetransport of oxygen and are optically clear, strong and hydrophilic.

The present invention provides materials which can be usefully employedfor the fabrication of prostheses such as heart valves and intraocularlenses, as optical contact lenses or as films. More particularly, thepresent invention concerns contact lenses.

The present invention further provides articles of manufacture which canbe used for biomedical devices, such as, surgical devices, heart valves,vessel substitutes, intrauterine devices, membranes and other films,diaphragms, surgical implants, blood vessels, artificial ureters,artificial breast tissue and membranes intended to come into contactwith body fluid outside of the body, e.g., membranes for kidney dialysisand heart/lung machines and the like, catheters, mouth guards, dentureliners, intraocular devices and especially contact lenses.

It is known that blood, for example, is readily and rapidly damaged whenit comes into contact with artificial surfaces. The design of asynthetic surface which is antithrombogenic and nonhemolytic to blood isnecessary for prostheses and devices used with blood.

The present invention also provides a method of surface modifyingcontact lenses and like medical devices through the use of complementaryreactive functionality. Although only contact lenses will be referred tohereinafter for purposes of simplicity, such reference is not intendedto be limiting since the subject method is suitable for surfacemodification of other medical devices as well as contact lenses.Reactive hydrophilic polymers are used to form covalent chemicallinkages with the surface of contact lenses manufactured from thereactive functionalized fumaric- and itaconic-containing prepolymers ofthe invention herein. The preferred reactive, hydrophilic polymers foruse in the present invention are selected based on the specific reactivefunctionalized fumaric- and itaconic-containing polymeric material to becoated. In accordance with the present invention, the one or morereactive hydrophilic polymers selected for surface modification musthave complementary chemical functionality to that of the reactivefunctionalized fumaric- and itaconic-containing polymeric materials.Such complementary chemical functionality enables a chemical reactionbetween the reactive functionalized fumaric- and itaconic-containingpolymeric material and the reactive hydrophilic polymer to form covalentchemical linkages therebetween. The one or more reactive hydrophilicpolymers are thus chemically bound to the surface of the one or morereactive functionalized fumaric- and itaconic-containing polymericmaterials of the contact lens or like medical device to achieve surfacemodification thereof. For surface modification of contact lenses inaccordance with the present invention, complementary reactivefunctionality is incorporated between the reactive functionalizedfumaric- and itaconic-containing prepolymers of the contact lensmaterial and the surface modification treatment polymer (SMTP). Forexample, if a reactive hydrophilic SMTP has epoxide functionality, thenthe contact lens material to be treated must have a functionalizedfumaric- or itaconic-containing prepolymer having a residue withcomplementary functionality that will react with that of the SMTP. Insuch a case, the contact lens material could include a reactivefunctionalized fumaric-containing prepolymer such as bis-α,ω-fumarylbutyl polydimethyl siloxane, diacid to react with the SMTP epoxidefunctionality. Likewise, if a contact lens is formed from functionalizedfumaric-containing material having a residue providing epoxide reactive,a hydrophilic SMTP containing a 2-hydroxyethyl methacrylate copolymercould be used for surface modification in accordance with the presentinvention. Examples of complementary functionality are provided below inTable 1.

TABLE 1 RESIDUE HAVING A REACTIVE COMPLEMENTARY FUNCTIONAL GROUPFUNCTIONALITY Carboxylic acid, isocyanate, epoxy, Alcohol, amine, thiolanhydride, lactone, lactam, oxazolone Glycidyl methacrylate (epoxy),Carboxylic Acid anhydride, amine, alcohol Amine, thiol, alcoholOxazolone Carboxylic acid, alcohol, primary Anhydride amine, thiolAlcohol, carboxylic acid, amine EpoxideMore specifically, surface modification of contact lenses havingreactive functionalized fumaric- and itaconic-containing copolymers inaccordance with the present invention requires one or more reactive,hydrophilic SMTPs. The reactive hydrophilic SMTPs useful in the practiceof the present invention are copolymers of various hydrophilic monomerswith a monomer having reactive chemical functionality. The hydrophilicmonomers can be aprotic types such as acrylamides and N-vinylpyrrolidinone or protic types such as methacrylic acid and2-hydroxyethyl methacrylate. Examples of suitable hydrophilic monomersinclude, but are not limited to, N,N-dimethylacrylamide,N,N-dimethylmethacrylamide, N-methylmethacrylamide andN-methylacrylamide; but preferably N,N-dimethylacrylamide for increasedhydrophilicity. Suitable monomers having reactive chemical functionalityinclude for example, but are not limited to, monomers having epoxide,carboxylic acid, anhydride, oxazolone and alcohol functionalities.Examples of suitable reactive, hydrophilic SMTPs include, but are notlimited to, copolymers and terpolymers of the monomers having reactivechemical functionality described above. Such reactive, hydrophilic SMTPsare produced through free radical polymerization techniques known tothose skilled in the art.

Although the teachings of the present invention are preferably appliedto soft or foldable contact lenses or like medical devices formed of afoldable or compressible material, the same may also be applied toharder, less flexible, lenses formed of a relatively rigid material suchas poly(methyl methacrylate) (PMMA).

In accordance with the present invention, the reactive functionalizedfumaric- and itaconic-containing prepolymers are used to produce acontact lens containing reactive functional groups. One or morereactive, hydrophilic SMTPs as described above, are then selected so asto have chemical functionality complementary to that of the reactivefunctionalized fumaric- and itaconic-containing prepolymers comprisingthe contact lens. Such complementary chemical functionality enables achemical reaction to occur between the functional groups of the reactivefunctionalized fumaric- and itaconic-containing prepolymer forming thecontact lens and the functional groups of the one or more reactive,hydrophilic SMTPs. This chemical reaction between functional groupsforms covalent chemical linkages therebetween. For example, a contactlens containing functionalized prepolymer having hydroxyl functionalgroups would preferably undergo surface modification using reactive,hydrophilic SMTPs containing carboxylic acid functional groups,isocyanate functional groups or epoxy functional groups. Likewise, acontact lens containing functionalized prepolymer having carboxylic acidgroups would preferably undergo surface modification using reactive,hydrophilic SMTPs containing glycidyl methacrylate (GMA) monomer unitsto provide epoxy functional groups. The reaction of the contact lenscontaining functionalized fumaric- and itaconic-containing reactivefunctional groups and the reactive hydrophilic SMTPs is conducted underconditions known to those of skill in the art.

The reactive functionalized fumaric- and itaconic-containing prepolymersuseful in certain embodiments of the present invention may be preparedaccording to syntheses well known in the art and according to themethods disclosed in the following examples. Surface modification ofcontact lenses produced from one or more reactive functionalizedfumaric- and itaconic-containing polymeric materials using one or morereactive, hydrophilic SMTPs in accordance with the present invention isdescribed in still greater detail in the examples that follow.

EXAMPLES Example 1 Preparation of an Acid-terminated Fumaric Prepolymer[(F2D20-diacid)]

To a thoroughly dried 500-ml round bottom flask equipped with a refluxcondenser was added bis-α,ω-hydroxybutyl polydimethylsiloxane (Mn 1624,30.08 grams, 0.0185 mole) prepared by following a procedure described inJournal of Polymer Science, Part A. 33, 1773 (1995) and fumaryl chloride(MW 152.96, 6.4013 grams, 0.0418 moles) (Aldrich Chemical, Milwaukee,Wis.). The reaction mixture was heated with an oil bath at 60° C. Aftertwo hours, the reaction was complete, as indicated by the loss of CH₂—OHpeak at 3.5 ppm (in H-NMR). The content of the flask was stripped undervacuum (0.4 mmHg) at 80° C. for 2 hours. To the content was then added 3mg of water and 30 ml of THF. The mixture was heated under reflux untilall acid chloride groups disappeared (by IR 1769 cm⁻¹). THF was thenstripped from the mixture in a Rotavapor. The residue remaining was thenadded to 200 mL ether and extracted with 50 mL of water three times. Thefinal residue in ether was dried with magnesium sulfate and then vacuumstripped at 80° C. for two hours. SEC (polystyrene standard): Mn=2001,Mw=3141 (Pd=1.57).

Example 2 Preparation of an Acid-terminated Itaconate-polysiloxanePrepolymer (I2D20-diacid)

To a thoroughly dried 500-mL round bottom flask equipped with a refluxcondenser is added bis-α,ω-hydroxybutyl polydimethylsiloxane (Mn 1624,30.08 grams, 0.0185 mole) and itaconyl chloride (MW 166.99, 6.99 grams,0.0418 moles). The mixture is heated with an oil bath at 60° C. Aftertwo hours, the reaction is complete, as indicated by the loss of CH₂—OHpeak at 3.5 ppm (in H-NMR). The content of the flask is stripped undervacuum (<0.4 mmHg) at 80° C for 2 hours. To the content is then added 3mg of water and 30 mL of THF. The mixture is heated under reflux untilall acid chloride groups have disappeared totally (by IR 1769 cm⁻¹). THFis then stripped from the product in a Rotavapor. The residue remainingis then added to 200 mL ether and extracted with 50 mL of water threetimes. The final residue in ether is dried with magnesium sulfate andthen vacuum stripped at 80° C. for 2 hours.

Example 3 Preparation of an Acid-terminated Maleate-polysiloxanePrepolymer (M2D20-diacid)

To a thoroughly dried 500-mL round bottom flask equipped with a refluxcondenser is added bis-α,ω-hydroxybutyl polydimethylsiloxane (Mn 1624,30.08 grams, 0.0185 mole), 150 mL of tetrahydrofuran and maleicanhydride (MW 98.06, 4.10 grams, 0.0418 moles). The mixture is heatedwith an oil bath at 60° C. After sixteen hours, the reaction iscomplete, as indicated by the loss of CH₂—OH peak at 3.5 ppm (in H-NMR).To the content is then added 5 mL of water and continued heating for 2hours. The solution is dried with magnesium sulfate and then vacuumstripped at 80° C. for 2 hours to give product.

Example 4 Preparation of Hydrogel Films from Fumaric Prepolymer andOther Comonomers

A prepolymer prepared as described in Example 1, 32 parts, was mixedwith 32 parts of N,N-dimethylacrylamide, 36 parts of TRIS, 27 parts ofhexanol, and 0.3 part Darocur® 1173 initiator (Ciba Specialty Chemical).The mix was cast between two silane-treated glass plates and cured in anoven at 70° C. for an hour. The cured films were then released,extracted in isopropanol, boiled in water for 4 hours and then placed inborate buffered saline. Properties of hydrogel films: Water content 39%,Modulus 36 g/mm², Tear strength 13 g/mm. Oxygen permeability 93 (Dkunit).

Example 5 Hydrogel Film Preparation—Derived from the PrepolymerDescribed in Example 1. (Thermal Curing)

A monomer mix was prepared from a prepolymer prepared as described inExample 1, TRIS, DMA and Vazo® 52 initiator (DuPont) at the weight ratioof 20/40/40/1. The mix was then cast and processed into hydrogel filmsby applying the same procedure as described in Example 4. Properties ofhydrogel films: Water content 41%; Modulus 49 g/mm²; Tear strength 3.0g/mm; Oxygen permeability 63 (DK unit).

Example 6 Lens Casting with Variable Frequency Microwave Curing,Purified with Super Critical Fluid, Followed by Direct Coating

A monomer mix consisting of a prepolymer prepared as described inExample 1, a t-butylfumarate end-capped polydimethylsiloxane of Mn 1600,(F2D20), TRIS, DMA and n-hexanol at a ratio of 15/15/30/40/5 wasprepared. This mix was placed between two polypropylene molds and curedunder microwave conditions. After releasing from the molds, the lenseswere extracted with CO₂ super critical fluid. The lenses were thenplaced in a distilled water solution containing a hydrophilic polymerderived from glycidyl methacrylate, N, N-dimethyl acrylamide andoctafluoropentyl methacrylate (prepared as described in Example 9) andthen autoclaved for 30 minutes. The lenses were then transferred toclean vials containing borate buffered saline at pH 7.1 and autoclaved.All lenses before and after treatments with polymer coating werecharacterized for water content and surface analysis (by XPS). Theresults were as follows:

TABLE 2 % O1S % N1S % C1S % Si1S (anterior/ (anterior/ (anterior)(anterior/ % water posterior) posterior) posterior) posterior) Before43.6 19.54/19.30 4.03/4.35 62.91/63.13 13.52/13.22 Treat- ment After46.25 18.84/19.24  6.3/6.33 65.58/65.78 8.88/8.02 Treat- ment

Example 7 Preparation of Hydrogel Films from a Prepolymer and OtherComonomers (UV Curing)

A prepolymer as described in Example 2, 30 parts, is mixed with 30 partsof N,N-dimethylacrylamide (DMA), 40 parts of 3-methacyryloxypropyltris(trimethylsiloxy)silane (TRIS), 20 parts of Hexanol, and 0.3 part ofDarocur-1173. The mix is then cast between two silane-treated glassplates under UV at about 4000 microwatts for two hours. The cured filmsare then extracted with isopropanol overnight, followed by boiling inwater and then placed in borate buffered saline at pH 7.2 to givehydrogel films.

Example 8 Synthesis of Reactive, Hydrophilic Copolymer ofN,N-dimethylacrylamide (DMA) and Glycidyl Methacrylate (GMA)

DMA-co-GMA [x=86, y=14] To a 3 liter (L) reaction flask is addeddistilled N,N-dimethylacrylamide (DMA, 2 g, 1.92 moles), distilledglycidyl methacrylate (GMA, 48 g, 0.32 moles)2,2′-azobisisobutyronitrile (AIBN, 0.4 g, 0.0024 moles) andtetrahydrofuran (2000 ml). The reaction vessel is fitted with amechanical stirrer, condenser, thermal controller and a nitrogen inlet.Nitrogen is bubbled through the solution for 15 minutes to remove anydissolved oxygen. The reaction flask is then heated to 60° C. under apassive blanket of nitrogen for 24 hours. The reaction mixture is thenadded slowly to 12 L of ethyl ether with good mechanical stirring. Thereactive polymer precipitates and is collected by vacuum filtration. Thesolid is placed in a vacuum oven at 30° C. overnight to remove the etherleaving the reactive polymer. The reactive polymer is placed in adesiccator for storage until use.

Example 9 Synthesis of Reactive, Hydrophilic Copolymer ofN,N-dimethylacrylamide (DMA), 1H,1H,5H-octafluoropentyl Methacrylate(OFPMA) and Glycidyl Methacrylate (GMA)

To a 1000 ml reaction flask is added distilled N,N-dimethylacrylamide(DMA, 64 g, 0.64 moles), 1H, 1H, 5H-octafluoropentyl methacrylate(OFPMA, 4 g, 0.012 moles, used as received), distilled glycidylmethacrylate (GM, 16 g, 0.112 moles) 2,2′-azobisisobutyronitrile (AIBN,0.12 g, 0.00072 moles) and tetrahydrofuran (1200 ml). The reactionvessel is fitted with a magnetic stirrer, condenser, thermal controllerand a nitrogen inlet. Nitrogen is bubbled through the solution for 15minutes to remove any dissolved oxygen. The reaction flask is thenheated to 60° C. under a passive blanket of nitrogen for 20 hours. Thereaction mixture is then added slowly to 6 L of ethyl ether with goodmechanical stirring. The reactive polymer precipitates and is collectedby vacuum filtration. The solid is placed in a vacuum oven at 30° C.overnight to remove the ether leaving 66.1 g of reactive polymer (79%yield). The reactive polymer is placed in a desiccator for storage untiluse.

Example 10 Synthesis of Reactive, Hydrophilic Copolymer ofN,N-dimethylacrylamide (DMA), 1H, 1H, 5H-octafluoropentyl Methacrylate(OFPMA), Glycidyl Methacrylate (GMA) and Polyethylene Glycol 1000Monomethylether Methacrylate (PEGMA)

To a 500 ml reaction flask is added distilled N,N-dimethylacrylamide(DMA, 8 g, 0.08 moles), 1H, 1H, 5H-octafluoropentyl methacrylate (OFPMA,1 g, 0.003 moles, used as received), distilled glycidyl methacrylate(GM, 4 g, 0.028 moles) Polyethylene glycol 1000 monomethylethermethacrylate (PEGMA, 8 g, 0.007 moles), 2,2′-azobisisobutyronitrile(AIBN, 0.03 g, 0.00018 moles) and tetrahydrofuran (300 ml). The reactionvessel is fitted with a magnetic stirrer, condenser, thermal controllerand a nitrogen inlet. Nitrogen is bubbled through the solution for 15minutes to remove any dissolved oxygen. The reaction flask is thenheated to 60° C. under a passive blanket of nitrogen for 72 hours. Flashevaporation of the solvent followed by freeze drying leaves the reactivepolymer, a wax like semi-solid.

Example 11 Synthesis of Reactive, Hydrophilic Copolymer ofN-Vinyl-2-pyrrolidinone (NVP) and 4-Vinylcyclohexyl-1,2-epoxide (VCHE)

To a 1 L reaction flask is added distilled N-vinyl-2-pyrrolidinone (NVP,53.79 g, 0.48 moles), 4-vinylcyclohexyl-1,2-epoxide (VCHE, 10.43 g,0.084 moles), 2,2′-azobisisobutyronitrile (AIBN, 0.05 g, 0.0003 moles)and THF (600 ml). The reaction vessel is fitted with a magnetic stirrer,condenser, thermal controller and a nitrogen inlet. Nitrogen is bubbledthrough the solution for 15 minutes to remove any dissolved oxygen. Thereaction flask is then heated to 60° C. under a passive blanket ofnitrogen for 20 hours. The reaction mixture is then added slowly to 6 Lof ethyl ether with good mechanical stirring. The copolymer precipitatesand is collected by vacuum filtration. The solid is placed in a vacuumoven at 30° C. overnight to remove the ether leaving the reactivepolymer. The reactive polymer is placed in a desiccator for storageuntil use.

Example 12 Synthesis of A Reactive Hydrophilic Copolymer ofN,N-dimethylacrylamide (DMA), Lauryl Methacrylate (LMA) and GlycidylMethacrylate (GMA)

To a 1000 ml reaction flask is added distilled N,N-dimethylacrylamide(DMA, 32 g, 0.32 moles), lauryl methacrylate (LMA, 1.5 g, 0.006 moles,used as received), distilled glycidyl methacrylate (GM, 8 g, 0.056moles) 2,2′-azobisisobutyronitrile (AIBN, 0.06 g, 0.00036 moles) andtetrahydrofuran (600 ml). The reaction vessel is fitted with a magneticstirrer, condenser, thermal controller and a nitrogen inlet. Nitrogen isbubbled through the solution for 15 minutes to remove any dissolvedoxygen. The reaction flask is then heated to 60° C. under a passiveblanket of nitrogen for 20 hours. The reaction mixture is then addedslowly to 3 L of ethyl ether with good mechanical stirring. The reactivepolymer precipitates and is collected by vacuum filtration. The solid isplaced in a vacuum oven at 30° C. overnight to remove the ether leavingthe reactive polymer. The reactive polymer is placed in a desiccator forstorage until use.

Example 13 Synthesis of Reactive, Hydrophilic Copolymer ofN,N-dimethylacrylamide (DMA) and Methacrylic Acid (MMA)

To a 3000 ml reaction flask is added distilled N,N-dimethylacrylamide(DMA, 128 g, 1.28 moles), methacrylic acid (MM, 32 g, 0.37 moles)2,2′-azobisisobutyronitrile (AIBN, 0.24 g, 0.0016 moles) and anhydrous2-propanol (2000 ml). The reaction vessel is fitted with a magneticstirrer, condenser, thermal controller and a nitrogen inlet. Nitrogen isbubbled through the solution for 15 minutes to remove any dissolvedoxygen. The reaction flask is then heated to 60° C. under a passiveblanket of nitrogen for 72 hours. The volume of the reaction mixture isreduced to half by flash evaporation. The reactive polymer isprecipitated into 8L of ethyl ether and then collected by vacuumfiltration. The solid is placed in a vacuum oven at 30° C. overnight toremove the ether leaving the reactive polymer. The reactive polymer isplaced in a desiccator for storage until use.

Example 14 Synthesis of a Hydrophilic Reactive Polymer ofN,N-dimethylacrylamide (DMA) and 12-Methacryloyloxydodecanoic Acid(LMAA)

To a 500 ml reaction flask is added distilled N,N-dimethylacrylamide(DMA, 15.2 g, 0.153 moles), 12-methacryloyloxydodecanoic acid (LMAA, 4.8g, 0.017 moles) 2,2′-azobisisobutyronitrile (AIBN, 0.032 g, 0.0002moles) and anhydrous tetrahydrofuran (200 ml). The reaction vessel isfitted with a magnetic stirrer, condenser, thermal controller and anitrogen inlet. Nitrogen is bubbled through the solution for 15 minutesto remove any dissolved oxygen. The reaction flask is then heated to 60°C. under a passive blanket of nitrogen for 72 hours. The reactionmixture is then added slowly to 2.5L of heptane with good mechanicalstirring. The reactive polymer precipitates and is collected by vacuumfiltration. The solid is placed in a vacuum oven at 30° C. overnight toremove the ether leaving the reactive polymer. The reactive polymer isplaced in a desiccator for storage until use.

Contact lenses manufactured using the unique materials of the presentinvention are used as customary in the field of ophthalmology. Whilethere is shown and described herein certain specific structures andcompositions of the present invention, it will be manifest to thoseskilled in the art that various modifications may be made withoutdeparting from the spirit and scope of the underlying inventive conceptand that the same is not limited to particular structures herein shownand described except insofar as indicated by the scope of the appendedclaims.

1. A method of forming a surface modified medical device, the methodcomprising: providing a medical device comprising a copolymer preparedby polymerizing a monomer mixture comprising, (A) 20 to 80 weight % ofat least one prepolymer selected from the group consisting of compoundshaving the following formula:YCO—CH═CHCOW(R₁)_(n)(SiR₂R₃O)_(m)(SiR₂R₃)(R₁)_(n)WOCCH═CH—COYandCH₂═C(CH₂COY)COW(R₁)_(n)(SiR₂R₃O)_(m)(SiR₂R₃)(R₁)_(n)WOC(CH₂COY)C═CH₂wherein R₁ is selected from the group consisting of alkylenes andalkylenes containing ether linkages, R₂ and R₃ are independentlyselected from the group consisting of alkyl groups, phenyl groups, alkylgroups substituted with halogen, phenyl groups substituted with halogen,alkyl groups containing ether linkages and phenyl groups containingether linkages, W is O or NH, n is an integer between 1 and 10, m is aninteger between 2 and 200, and Y is a residue having a reactivefunctional group selected from the group consisting of hydroxyl,carboxyl, oxazolone, epoxy and anhydride functional groups, and (B) 5 to50 weight % of at least one copolymerizable device-forming monomer,contacting a surface of the device with a solution containing a surfacemodifying agent having functionality complementary to the functionalizedsilicone-containing copolymer; and subjecting the device surface andsurface modifying agent to reaction conditions suitable for forming acovalent bond between the functionalized silicone-containing copolymerand the surface modifying agent having functionality complementary tothe functionalized silicone-containing copolymer while the surfacemodifying agent is in contact with the device surface to form a surfacemodified medical device.
 2. The method of claim 1 wherein R₁ contains 1to 10 carbon atoms.
 3. The method of claim 1 wherein the copolymerprepared by polymerizing a monomer mixture further comprises, 10 to 50weight % of at least one additional silicone-containing monomer and 10to 50 weight % of at least one copolymerizable device-forminghydrophilic monomer.
 4. The method of claim 1 wherein, component (A) hasthe following formula:YCO—CH═CHCOW(R₁)_(n)(SiR₂R₃O)_(m)(SiR₂R₃)(R₁)_(n)WOCCH═CH—COY wherein R₁is selected from the group consisting of alkylenes and alkylenescontaining ether linkages, R₂ and R₃ are methyl, n is 4, m is an integerbetween 5 and 200, W is O, and Y is OH and is in a trans configuration.5. The method of claim 1 wherein, component (A) has the followingformula:CH₂═C(CH₂COY)COW(R₁)_(n)(SiR₂R₃O)_(m)(SiR₂R₃)(R₁)_(n)WOC(CH₂COY)C═CH₂wherein R₁ is selected from the group consisting of alkylenes andalkylenes containing ether linkages, R₂ and R₃ are methyl, n is 4, m isan integer between 5 and 200, W is O, and Y is OH.
 6. The method ofclaim 1 wherein, component (A) has the following formula:YCO—CH═CHCOW(R₁)_(n)(SiR₂R₃O)_(m)(SiR₂R₃)(R₁)_(n)WOCCH═CH—COY wherein R₁is selected from the group consisting of alkylenes and alkylenescontaining ether linkages, R₂ and R₃ are methyl, n is 4, m is an integerbetween 5 and 200, W is O, and Y is OH and is in a cis configuration. 7.The method of claim 1 wherein the medical device formed is selected fromthe group consisting of heart valves, intraocular lenses, contactlenses, intrauterine devices, vessel substitutes, artificial ureters andartificial breast tissue.
 8. The method of claim 7 wherein the medicaldevice formed is a contact lens.
 9. The method of claim 8 wherein themedical device formed is a soft contact lens.
 10. The method of claim 3wherein, component (A) has the following formula:YCO—CH═CHCOW(R₁)_(n)(SiR₂R₃O)_(m)(SiR₂R₃)(R₁)_(n)WOCCH═CH—COY wherein R₁is selected from the group consisting of alkylenes and alkylenescontaining ether linkages, R₂ and R₃ are methyl, n is 4, m is an integerbetween 5 and 200, W is O and Y is OH and is in a trans configuration.11. The method of claim 3 wherein, component (A) has the followingformula:CH₂═C(CH₂COY)COW(R₁)_(n)(SiR₂R₃O)_(m)(SiR₂R₃)(R₁)_(n)WOC(CH₂COY)C═CH₂wherein R₁ is selected from the group consisting of alkylenes andalkylenes containing ether linkages, R₂ and R₃ are methyl, n is 4, m isan integer between 5 and 200, W is O and Y is OH.
 12. The method ofclaim 3 wherein, component (A) has the following formula:YCO—CH═CHCOW(R₁)_(n)(SiR₂R₃O)_(m)(SiR₂R₃)(R₁)_(n)WOCCH═CH—COY wherein R₁is selected from the group consisting of alkylenes and alkylenescontaining ether linkages, R₂ and R₃ are methyl, n is 4, m is an integerbetween 5 and 200, W is O, and Y is OH and is in a cis configuration.13. The method of claim 3 wherein the medical device formed is selectedfrom the group consisting of heart valves, intraocular lenses, contactlenses, intrauterine devices, vessel substitutes, artificial ureters andartificial breast tissue.
 14. The method of claim 13 wherein the medicaldevice formed is a contact lens.
 15. The method of claim 14 wherein themedical device formed is a soft contact lens.